苯丙胺 Pan-SHIP1/2 抑制剂：作为抗肿瘤剂的合成及初步生物学评价。

-Benzyl Tryptamine Pan-SHIP1/2 Inhibitors: Synthesis and Preliminary Biological Evaluation as Anti-Tumor Agents.

机构信息

Department of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.

Department of Chemistry, Syracuse University, Syracuse, NY 13244, USA.

出版信息

Molecules. 2022 Dec 2;27(23):8451. doi: 10.3390/molecules27238451.

DOI:10.3390/molecules27238451

PMID:36500543

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9738565/

Abstract

Inhibition of phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP) with small molecule inhibitors leads to apoptosis in tumor cells. Inhibitors that target both SHIP1 and SHIP2 (pan-SHIP1/2 inhibitors) may have benefits in these areas since paralog compensation is not possible when both SHIP paralogs are being inhibited. A series of tryptamine-based pan-SHIP1/2 inhibitors have been synthesized and evaluated for their ability to inhibit the SHIP paralogs. The most active compounds were also evaluated for their effects on cancer cell lines.

摘要

小分子抑制剂抑制磷脂酰肌醇 3,4,5-三磷酸 5-磷酸酶 (SHIP) 可导致肿瘤细胞凋亡。靶向 SHIP1 和 SHIP2 的抑制剂（pan-SHIP1/2 抑制剂）可能具有这些优势，因为当同时抑制两个 SHIP 同源物时，不可能发生同源物补偿。已经合成了一系列基于色胺的 pan-SHIP1/2 抑制剂，并评估了它们抑制 SHIP 同源物的能力。最活跃的化合物还评估了它们对癌细胞系的影响。